Atypical fracture of the femur in a patient using denosumab – a case report

Schilcher, Jörg; Aspenberg, Per

doi:10.3109/17453674.2014.885355

Cited by 60 publications

(35 citation statements)

References 5 publications

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“…Only one case did not involve any prior bisphosphonate use, but this patient also had chronic kidney disease [5]. Two patients had bilateral AFF separated by time intervals of one and five years, respectively [8,9]. It remains unknown how long a person who has suffered an AFF will continue to be at risk for a second AFF; indeed, many second AFFs have occurred some years after the initial ones.…”

Section: Discussionmentioning

confidence: 92%

“…Parapodis et al [5] reported an 81-year-old woman who sustained a unilateral subtrochanteric fracture after receiving one dose of denosumab for treatment of osteopenia on a background of chronic kidney disease and hyperparathyroidism. However, it has been argued that her fracture did not meet the radiographic criteria for an atypical fracture [9]. The second report was on a 59-year-old woman with a history of rheumatoid arthritis and osteoporosis who sustained an atypical fracture of her right femur three months after starting denosumab and after having been on alendronate for five years but was discontinued four years prior to the fracture [6].…”

Section: Discussionmentioning

confidence: 98%

“…Prior to the denosumab therapy, she had received oral alendronate and strontium renolate for short periods of time. The fifth case involved an 83-year-old woman who had bilateral AFF with a time interval of five years between fractures [9]. The first episode occurred while she was taking alendronate and the second 29 months after the last zoledronate injection and after 16 months on denosumab therapy.…”

Section: Discussionmentioning

confidence: 99%

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Atypical femoral fracture in a patient treated with denosumab

Khow

Yong

2014

J Bone Miner Metab

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Atypical fractures of the femur (AFF) have been reported in the literature at an increasing rate over the past decade, especially in patients who have been on prolonged courses of bisphosphonates. However, there have only been a few reported cases of AFF in those treated with other antiresorptive medications. In this case report, a 72-year-old woman with chronic obstructive pulmonary disease and osteoporosis presented with an atraumatic right femoral fracture in the setting of denosumab use. In contrast with other reports, this patient had received bisphosphonate therapy for a short duration before the switch to denosumab. While causality between the fracture and denosumab use cannot be established in this case, there is a growing number of reports of a similar association. Ongoing vigilance is required to determine whether denosumab is associated with or potentially a cause of AFF.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Atypical femoral fracture in a patient treated with denosumab

Khow

Yong

2014

J Bone Miner Metab

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“…The inhibition of bone remodeling can impair the reparation of microcracks and incomplete stress fractures, finally resulting in complete fractures. These fractures have been reported in patients taking bisphosphonates and denosumab, but they can also occur in patients not exposed to these drugs [100,101 ] . Odvina et al [102 ] were the first to propose a possible relation between prolonged use of bisphosphonates and atypical fractures.…”

Section: Atypical Femoral Fractures (Aff)mentioning

confidence: 87%

Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

López-Delgado¹,

Riancho‐Zarrabeitia²,

Riancho³

2016

Expert Opinion on Drug Metabolism & Toxicology

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“…One of the reasons is that both bisphosphonates and denosumab mainly target osteoclasts, but not proliferative NSCs (20). On the other side, stress fracture is associated with the long-term use of antiresorptive medications, such as denosumab and bisphosphonate (34,35). Therefore, the suppression of both osteoclast formation and NSC growth could be a promising strategy for curing GCTB.…”

Section: Discussionmentioning

confidence: 99%

Bortezomib Inhibits Giant Cell Tumor of Bone through Induction of Cell Apoptosis and Inhibition of Osteoclast Recruitment, Giant Cell Formation, and Bone Resorption

Luo

Jin

et al. 2016

Molecular Cancer Therapeutics

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Giant cell tumor of bone (GCTB) is a rare and highly osteolytic bone tumor that usually leads to an extensive bone lesion. The purpose of this study was to discover novel therapeutic targets and identify potential agents for treating GCTB. After screening the serum cytokine profiles in 52 GCTB patients and 10 normal individuals using the ELISA assay, we found that NF-kB signaling-related cytokines, including TNFa, MCP-1, IL1a, and IL17A, were significantly increased in GCTB patients. The results were confirmed by IHC that the expression and activity of p65 were significantly increased in GCTB patients. Moreover, all of the NF-kB inhibitors tested suppressed GCTB cell growth, and bortezomib (Velcade), a well-known proteasome inhibitor, was the most potent inhibitor in blocking GCTB cells growth. Our results showed that bortezomib not only induced GCTB neoplastic stromal cell (NSC) apoptosis, but also suppressed GCTB NSC-induced giant cell differentiation, formation, and resorption. Moreover, bortezomib specifically suppressed GCTB NSC-induced preosteoclast recruitment. Furthermore, bortezomib ameliorated GCTB cellinduced bone destruction in vivo. As a result, bortezomib suppressed NF-kB-regulated gene expression in GCTB NSC apoptosis, monocyte migration, angiogenesis, and osteoclastogenesis. Particularly, the inhibitory effects of bortezomib were much better than zoledronic acid, a drug currently used in treating GCTB, in our in vitro experimental paradigms. Together, our results demonstrated that NF-kB signaling pathway is highly activated in GCTB, and bortezomib could suppress GCTB and osteolysis in vivo and in vitro, indicating that bortezomib is a potential agent in the treatment of GCTB.

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Atypical fracture of the femur in a patient using denosumab – a case report

Cited by 60 publications

References 5 publications

Atypical femoral fracture in a patient treated with denosumab

Atypical femoral fracture in a patient treated with denosumab

Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

Bortezomib Inhibits Giant Cell Tumor of Bone through Induction of Cell Apoptosis and Inhibition of Osteoclast Recruitment, Giant Cell Formation, and Bone Resorption

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